Telocytes and stem cells: a tandem in cardiac regenerative medicine
Lawrence M. Popescu
Department of Cellular and Molecular Medicine, Carol Davila University of Medicine and Pharmacy, P.O. Box 35-29, Bucharest 35, Romania
Abstract:
Telocytes (TC) are cells with telopodes (Tp). TC have a small cell body, but characteristic prolongations that we named Tp. TC represent a novel type of interstitial (stromal) cells recently described in several cavitary and non-cavitary organs, including human heart with its three concentric layers: endo-, myo- and epi-cardium (see www.telocytes.com). Tp are particular prolongations being characterized by: a) number (1-5, frequently: 2-3); b) length (tens up to hundreds of μm); c) moniliform aspect - an alternation of dilated segments (podoms) and thin segments (podomeres) < 200 nm thickness, below the resolving power of light microscopy; d) podoms accommodate mitochondria, ER and caveolae, the so-called "Ca2+ uptake/release units"; e) branching in dichotomous pattern making a 3D network, a labyrinthic system with complex ultrastructural junctions. Electron microscope tomography revealed particular junctions between TC and cardiomyocytes. Such junctions cannot be found by usual Electron Microscopy. At the level of epicardium, we identified by electron microscopy the so-called cardiac stem cell niches (CSCN). Such CSCN contain, inter alia, TC and cardiomyocytes progenitors and precursors. Noteworthy, Tp surrounds cardiac progenitors or precursors and guide them to form the coherent 3D myocardial architecture. Apparently, Tp provide "tracks" for the sliding of cardiomyocytes precursors in their development and integration as working cardiomyocytes. Using an experimental model (rat) of myocardial infarction we found by electron microscopy 4 lesional stages: i) the first day, many eosinophils (inflammation); ii) after 2 days, many fibroblasts producing fibrosis; iii) after one week, myofibroblasts starting matrix remodeling; iv) after one month, numerous telocytes and myocadium remodeling and neo-vascularization. Is to be mentioned that telocytes isolated in cell culture secrete VEGF and cyto- / chemo-kines as revealed by SELDI-TOF Mass Spectometry and xMAP Technology (Luminex). In conclusion, in the adult mammalian heart, TCs along the stem cells and cardiomyocyte progenitors sustain a continuous cardiac renewal process, and might be key-players in repairing the damaged heart. The tandem telocytes-stem cells could be a better option for therapy rather than stem cells alone.
